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2003:
50 Years of the Double Helix

International Consortium
Completes Human Genome Project

All Goals Achieved; New Vision for Genome Research Unveiled

BETHESDA, Md., April 14,
2003 –
The International Human Genome Sequencing Consortium, led in the United
States by the National Human Genome Research Institute (NHGRI) and the Department
of Energy (DOE), today announced the successful completion of the Human Genome
Project more than two years ahead of schedule.

Also today, NHGRI unveiled its bold new vision for the future of genome
research, officially ushering in the era of the genome. The vision will be
published in the April 24 issue of the journal Nature, coinciding with the
50th anniversary of Nature’s publication of the landmark paper by Nobel
laureates James Watson and Francis Crick that described DNA’s double
helix. Dr. Watson also was the first leader of the Human Genome Project.

The international effort to sequence the 3 billion DNA letters in the human
genome is considered by many to be one of the most ambitious scientific undertakings
of all time, even compared to splitting the atom or going to the moon.

“The Human Genome Project has been an amazing adventure into ourselves,
to understand our own DNA instruction book, the shared inheritance of all
humankind," said NHGRI Director Francis S. Collins, M.D., Ph.D., leader
of the Human Genome Project since 1993. "All of the project’s
goals have been completed successfully – well in advance of the original
deadline and for a cost substantially less than the original estimates.”

Aristides Patrinos, Ph.D., director of DOE’s Office of Biological
and Environmental Research in the Office of Science, said, “Sequencing
the human genome was a pioneering venture with risks and uncertainties. But
its success has created a revolution – transforming biological science
far beyond what we could imagine. We have opened the door into a vast and
complex new biological landscape. Exploring it will require even more creative
thinking and new generations of technologies.”

The flagship effort of the Human Genome Project has been producing the reference
sequence of the human genome. The international consortium announced the
first draft of the human sequence in June 2000. Since then, researchers have
worked tirelessly to convert the “draft” sequence into a “finished” sequence.
Finished sequence is a technical term meaning that the sequence is highly
accurate (with fewer than one error per 10,000 letters) and highly contiguous
(with the only remaining gaps corresponding to regions whose sequence cannot
be reliably resolved with current technology). That standard was first achieved
for a human chromosome when a team of British, Japanese and U.S. researchers
produced a finished sequence for human chromosome 22 in 1999.

The finished sequence produced by the Human Genome Project covers about
99 percent of the human genome's gene-containing regions, and it has been
sequenced to an accuracy of 99.99 percent. In addition, to help researchers
better understand the meaning of the human genetic instruction book, the
project took on a wide range of other goals, from sequencing the genomes
of model organisms to developing new technologies to study whole genomes.
As of April 14, 2003, all of the Human Genome Project’s ambitious goals
have been met or surpassed. (HGP Goals)

When the Human Genome Project was launched in 1990, many in the scientific
community were deeply skeptical about whether the project’s audacious
goals could be achieved, particularly given its hard-charging timeline and
relatively tight spending levels. At the outset, the U.S. Congress was told
the project would cost about $3 billion in FY 1991 dollars and would be completed
by the end of 2005. In actuality, the Human Genome Project was finished two
and a half years ahead of time and, at $2.7 billion in FY 1991 dollars, significantly
under original spending projections. (HGP Budget)

“Never would I have dreamed in 1953 that my scientific life would
encompass the path from DNA’s double helix to the 3 billion steps of
the human genome. But when the opportunity arose to sequence the human genome,
I knew it was something that could be done – and that must be done,” said
Nobel Laureate James D. Watson, Ph.D., president of Cold Spring Harbor Laboratory
in Cold Spring Harbor, N.Y. “The completion of the Human Genome Project
is a truly momentous occasion for every human being around the globe.”

Besides delivering on the stated goals, the international network of researchers
has produced an amazing array of advances that most scientists had not expected
until much later. These "bonus" accomplishments include: an advanced
draft of the mouse genome sequence, published in December 2002; an initial
draft of the rat genome sequence, produced in November 2002; the identification
of more than 3 million human genetic variations, called single nucleotide
polymorphisms (SNPs); and the generation of full-length complementary DNAs
(cDNAs) for more than 70 percent of known human and mouse genes.

The International Human Genome Sequencing Consortium included hundreds of
scientists at 20 sequencing centers in China, France, Germany, Great Britain,
Japan and the United States. The five institutions that generated the most
sequence were: Baylor College of Medicine, Houston; Washington University
School of Medicine, St. Louis; Whitehead Institute/MIT Center for Genome
Research, Cambridge, Mass.; DOE’s Joint Genome Institute, Walnut Creek,
Calif.; and The Wellcome Trust Sanger Institute near Cambridge, England.
(See List)

“The enormity of the Human Genome Project is unprecedented in biology.
The international vision and collaboration of the scientists involved played
a crucial role in the project’s success,” said Mark Walport,
M.D., director designate of The Wellcome Trust, which led the Human Genome
Project in the United Kingdom. “The genome is the common thread that
connects us all, so it is only fitting that the sequence has been given to
us by scientists from all corners of the earth.”

All of the sequence data generated by the Human Genome Project has been
swiftly deposited into public databases and made freely available to scientists
around the world, with no restrictions on its use or redistribution. The
information is scanned daily by researchers in academia and industry, as
well as by commercial database companies providing information services to
biotechnologists.

“From the beginning, one of the operating principles of the Human
Genome Project has been that the data and resources it has generated should
rapidly be made available to the entire scientific community,” said
Robert Waterston, M.D., Ph.D., of the University of Washington, Seattle. “Not
only does the rapid release of data promote the best interests of science,
it also maximizes the benefits that the public receives from such research.”

In 1996, at a meeting in Bermuda, Dr. Waterston and John Sulston, Ph.D.,
then director of the Sanger Centre (now The Wellcome Trust Sanger Institute),
led the International Human Genome Sequencing Consortium to adopt the so-called “Bermuda
Principles,” which expressly call for automatic, rapid release of sequence
assemblies of 2,000 bases or greater to the public domain.

Scientists have been quick to mine this new trove of genomic data, as well
as to utilize the genomic tools and technologies developed by the Human Genome
Project. For example, when the Human Genome Project began in 1990, scientists
had discovered fewer than 100 human disease genes. Today, more than 1,400
disease genes have been identified.

For scientists seeking to understand the role of genetics in human health
and disease, the Human Genome Project's finished sequence represents a significant
advance over the "working draft" that was announced in June 2000.
The working draft covered 90 percent of the gene-containing part of the sequence,
28% of which had reached finished form, and contained about 150,000 gaps.
The finished version of the human genome now contains 99 percent of the gene-containing
sequence, with the missing parts essentially contained in less than 400 defined
gaps.

These remaining gaps represent regions of DNA in the genome with unusual
structures that cannot be reliably sequenced with current technology. These
regions, however, appear to contain very few genes. Closing these gaps will
require individual research projects and new technologies, rather than industrial-scale
efforts of the Human Genome Project. The high-throughput sequencing of the
human genome has thus reached its natural conclusion.

“This is the day that our planning group dreamed of,” said Bruce
Alberts, Ph.D., chairman of the 1988 National Research Council Committee
on Mapping and Sequencing the Human Genome, which produced the original recommendations
for the Human Genome Project. “And the quality of the sequence would
have amazed us. In 1988, we weren’t sure that accuracy rates of 99.9
percent were possible, and we were uncertain that continuity over distances
of millions of base pairs could be achieved. The finished human sequence
is a fabulous outcome. Biomedical researchers now have tremendous foundation
on which to build the science and medicine of the 21st century.” Dr.
Alberts is now the president of the National Academy of Sciences.

In addition to the improved accuracy, the average DNA letter now sits on
a stretch of
27,332,000 base pairs of uninterrupted, high-quality sequence – about
334 times longer than the 81,900 base-pair stretch that was available in
the working draft. Access to uninterrupted stretches of sequenced DNA can
make a major difference to researchers hunting for genes, dramatically cutting
the effort and expense required to search regions of the human genome that
may contain small and often rare mutations involved in disease.

"The Human Genome Project represents one of the remarkable achievements
in the history of science. Its culmination this month signals the beginning
of a new era in biomedical research,” said Eric Lander, Ph.D., director
of the Whitehead-MIT Center for Genome Research. “Biology is being
transformed into an information science, able to take comprehensive global
views of biological systems. With knowledge of all the components of the
cells, we will be able to tackle biological problems at their most fundamental
level.”

The essentially complete version of the human genome sequence also represents
a major boon to the growing field of comparative genomics: researchers are
attempting to learn more about human genetic makeup and function by comparing
our genomic sequence to that of other organisms, such as the mouse, the rat
or even the fruit fly.

“One of the most powerful tools for understanding our own genome is
to study it within the context of a much larger framework. That framework
is being created by ongoing efforts to sequence and analyze the genomes of
many other organisms,” said Richard Gibbs, Ph.D., director of Baylor
College of Medicine's Human Genome Sequencing Center. “As we identify
the similarities – and the differences – among the genes of mammals
and other organisms, we will begin to gain valuable new insights into human
evolution, as well as human health and disease.”

The impact of the Human Genome Project, however, extends far beyond laboratory
analysis. Under the guidance of Dr. Watson, the Human Genome Project became
the first large scientific undertaking to dedicate a portion of its budget
for research to the ethical, legal and social implications (ELSI) of its
work. NHGRI and DOE each set aside 3 to 5 percent of their genome budgets
to study how the exponential increase in knowledge about human genetic make-up
may affect individuals, institutions and society. An example of how ELSI
research has helped to inform public policy is the fact that more than 40
states in the United States have passed genetic non-discrimination bills,
many based on model language that grew out of this research. These efforts
will be even more crucial in the coming years as the results of genomic research
begin to appear in the clinic.

“Achieving the goals of the Human Genome Project is a historic milestone.
But this is no time to rest and relax,” said Dr. Collins. “With
this foundation of knowledge firmly in place, the medical advances promised
from the project can now be significantly accelerated.”

To spur such acceleration, NHGRI’s “A Vision for the Future
of Genomics Research” sets forth a series of "Grand Challenges" intended
to energize the scientific community in using the newfound understanding
of the genome to uncover the causes of disease and to develop bold new approaches
to the prevention and treatment of disease. The plan was the outcome of more
than a year of intense discussions with nearly 600 scientific and public
leaders from government, academia, non-profit organizations and the private
sector.

In the publication in Nature, the challenges facing genomic research are
depicted as a three-story house rising from the foundation of the Human Genome
Project. The three floors, representing the three major thrusts of this new
vision – Genomics to Biology, Genomics to Health and Genomics to Society – are
interconnected by vertical supports, representing computational biology,
ELSI, education, training, technology development and resources.

Many of the challenges in the vision are aimed at utilizing genome research
to combat disease and improve human health. The recommendations include calls
for researchers to work toward:

New tools to allow discovery in the near future of the hereditary
contributions to common diseases, such as diabetes, heart disease and mental
illness.

New methods for the early detection of disease.

New technologies that can sequence the entire genome of any person
for less than $1,000.

Wider access to tools and technologies of “chemical genomics” to
improve the understanding of biological pathways and accelerate drug discovery.

NHGRI and its partners in genome research have already begun tackling a
number of these challenges. For example, in November 2002, a team of researchers
from six nations launched the International HapMap Project, an effort to
produce a map of common human genetic variations aimed at speeding the search
for genes that contribute to cancer, diabetes, heart disease, schizophrenia
and many other common conditions.

"The
completion of the Human Genome Project should not be viewed as an end in
itself. Rather, it marks the start of an exciting new era – the era
of the genome in medicine and health," said Dr. Collins. "We firmly
believe the best is yet to come, and we urge all scientists and people around
the globe to join us in turning this vision into reality."

NHGRI’s U.S. partner in the Human Genome Project, DOE, has also developed
its own forward-looking plan for genome research. The DOE plan, published
in the April 11 issue of the journal Science, is focused on understanding
the ways in which microbes can provide new opportunities for developing clean
energy, reducing climate change and cleaning the environment. To achieve
that vision, DOE has begun the “Genomes to Life” program, which
will combine research in biology, engineering and computation with the development
of novel facilities for high-throughput biology projects.

NHGRI is one of the 27 institutes and centers at the National Institutes
of Health, an agency of the Department of Health and Human Services (DHHS).
Additional information about NHGRI can be found at its Web site, www.genome.gov.

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Human Genome Project 1990–2003

The Human Genome Project (HGP) was an international 13-year effort, 1990 to 2003. Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome. See Timeline for more HGP history.

Published from 1989 until 2002, this newsletter facilitated HGP communication, helped prevent duplication of research effort, and informed persons interested in genome research.

Citation and Credit

Unless otherwise noted, publications and webpages on this site were created for the U.S. Department of Energy Human Genome Project program and are in the public domain. Permission to use these documents is not needed, but credit the U.S. Department of Energy Human Genome Project and provide the URL http://www.ornl.gov/hgmis when using them. Materials provided by third parties are identified as such and not available for free use.